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International Immunology Advance Access originally published online on November 15, 2007
International Immunology 2008 20(1):89-104; doi:10.1093/intimm/dxm121
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Priming and stimulation of hepatitis C virus-specific CD4+ and CD8+ T cells against HCV antigens NS4, NS5a or NS5b from HCV-naive individuals: implications for prophylactic vaccine

Wen Li1,*, Deepa K. Krishnadas1,*, Rakesh Kumar2, D. Lorne J. Tyrrell3 and Babita Agrawal1

1 Department of Surgery
2 Department of Laboratory Medicine and Pathology
3 Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2S2, Canada

Correspondence to: B. Agrawal; E-mail: bagrawal{at}ualberta.ca

Hepatitis C virus (HCV) is a devastating human pathogen, yet there is no vaccine available for this virus. From studies with acute or chronic HCV-infected humans and chimpanzees, T-cell responses against HCV-derived conserved non-structural antigens have been correlated with viral clearance. In this study, recombinant adenoviral vectors containing HCV-derived NS4, NS5a or NS5b genes were employed to endogenously express the HCV antigens in human dendritic cells (DCs). The DCs expressing these HCV antigens exhibited normal phenotype and function. Intriguingly, we found that the DCs expressing HCV NS4, NS5a or NS5b antigens were able to significantly stimulate autologous T cells obtained from uninfected healthy individuals. These T cells produced various cytokines and proliferated in an HCV antigen-dependent manner. Evidence of both CD4+ and CD8+ T-cell responses generated in vitro against HCV NS4, NS5a or NS5b were obtained. HCV NS4 was much less stimulatory for CD4+ and CD8+ T cells than NS5. Further, in secondary assays, the CD4+ T cells primed in vitro exhibited HCV antigen-specific proliferative responses against recombinant protein antigens. In summary, we provide conclusive evidence of in vitro stimulation of CD4+ and CD8+ T cells from HCV-naive individuals against HCV antigens NS4, NS5a and NS5b. The studies with naive T cells represent early events in the induction of cellular immune responses, which most likely govern the outcome of HCV infection. These studies have significant implications in designing vaccines for HCV infection in both prophylactic and therapeutic settings.

Keywords: dendritic cells, hepatitis C virus, immune response, phenotype, T lymphocyte activation

* These authors contributed equally to this study.

Transmitting editor: A. Falus

Received 13 June 2007, accepted 17 October 2007.


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